This proposal seeks continuation of a successful training program in systemic autoimmunity at the Beth Israel Medical Deaconess Medical Center (BIDMC), Harvard Medical School (HMS). It requests support for three trainees each year to spend at least two years in the program. Trainees enter the program through one of the following tracks: Physicians who seek training in rheumatology or nephrology, physicians who enter other clinical fellowship programs including neurology and dermatology, physicians who have completed clinical training in a field relevant to systemic autoimmune diseases and PhDs with background in immunology, biochemistry and cell/molecular biology. The major criterion for selection is evidence of commitment to the study of systemic autoimmune diseases. Through this training physicians will develop skills in immunology and biology/biochemistry, whereas PhDs will become familiar with clinical issues pertinent to the study of systemic autoimmune diseases. Research activities will span studies in human and animal T cells, B cells, NKT cells, macrophages, mast cells, costimulation, immune cell signaling, immune tolerance, control of cytokine expression and function, pertinent aspects of regional immunology and biology (kidney, skin and nervous system), human genetics, immunodeficiency, complement and immunomodulation. The chief method of instruction involves personal involvement in a program of basic research under the close supervision of a faculty member. Moreover, a structured program of didactic courses in research seminars, journal clubs, research presentations in national and international meetings and grant writing is in place. The primary facilities for training are at BIDMC and HMS-affiliated institutions. The Program will be administered by the Program Director assisted by two senior experienced mentors, an administrator and three committees (Faculty, Internal and External Advisory) and evaluated through a rigorous process. Graduating trainees will be able to plan, seek funding and execute cutting edge research in systemic autoimmune diseases and will be properly tooled to develop new diagnostics and therapeutics.